Adaptation of Two Wild Bird-Origin H3N8 Avian Influenza Viruses to Mammalian Hosts

Abstract

Wild birds play an important role in the emergence, evolution, and spread of zoonotic avian influenza viruses (AIVs). However, there are few studies on the cross-species transmission of the H3N8 AIV originating from wild birds. In this study, we investigated the transmissibility and pathogenicity of two H3N8 low pathogenic avian influenza viruses (LPAIVs) isolated from wild birds, GZA1 and XJ47, to mammals. The HA genes of both strains belonged to Eurasian isolates, while the other genes were derived from a variety of other subtypes of AIVs. Both strains can infect specific-pathogen-free (SPF) chickens, BALB/c mice, and guinea pigs. The XJ47 strain spread horizontally in SPF chickens and guinea pigs. The GZA1 strain did not spread horizontally but caused higher weight loss and mild lung inflammation in mice. P12-GZA1- and P12-XJ47-adapted strains obtained after 12 passages in the lung of mice showed enhanced pathogenicity in mice, which led to obvious clinical symptoms, lung inflammation, and 100% death. Both adapted strains have the reported mutation T97I in the PA, and the reported mutation D701N in PB2 has been found in the P12-GZA1-adapted strain. This study provides an important scientific basis for the continuous monitoring of wild AIVs and the mechanism underlying AIV cross-species transmission.

Characterization of a human H3N8 influenza virus

“…Liang et al. 32 reported direct contact transmission to one of three guinea pigs for one of the viruses tested, but no transmission was observed for the second virus tested. Zhang et al.…”

“…Previously, two studies 31 , 32 tested the transmissibility of Eurasian avian H3N8 viruses (with gene compositions different from those of the novel reassortant H3N8 viruses) in guinea pigs and ferrets. Liang et al.…”

Genetic Characterization and Pathogenesis of Avian Influenza Virus H3N8 Isolated from Chinese pond heron in China in 2021

“…The genome-wide analysis of JX 5-1 reveals that its internal genes have a diverse variety of origins and that many of them are clustered with AIVs in Asian nations near China during the course of genetic evolution. Two H3N8 influenza viruses with wild bird origins—XJ47 and GZ—were shown to have comparable internal gene source dynamics to JX5-1 in a different investigation [ 58 ]. It is speculated that the migration of wild birds among Asian countries caused this frequent gene exchange.…”

“…The results of animal experiments showed low pathogenicity of JX5-1 in mice and inefficient replication of the virus in the lungs, indicating that the strain is not well adapted to mammals. In another study, both strains of wild bird-origin H3N8 avian influenza virus were able to replicate efficiently in mice and guinea pigs [ 58 ].…”

China faces the challenge of influenza A virus, including H3N8, in the post-COVID-19 era

“… 4 Our previous study confirmed that H3N8 could induce adaptive mammalian mutations. 5 AIV transmission from birds to humans is usually sporadic and occurs in specific contexts, mostly from contact with infected poultry or contaminated environments. However, owing to the widespread prevalence of this virus, more sporadic cases are expected in the future.…”